Mimicking the action of folding chaperones in molecular dynamics simulations: Application to the refinement of homology-based protein structures

Fan, H. and Mark, A. E. (2004) Mimicking the action of folding chaperones in molecular dynamics simulations: Application to the refinement of homology-based protein structures. Protein Science, 13 4: 992-999. doi:10.1110/ps.03449904


Author Fan, H.
Mark, A. E.
Title Mimicking the action of folding chaperones in molecular dynamics simulations: Application to the refinement of homology-based protein structures
Journal name Protein Science   Check publisher's open access policy
ISSN 0961-8368
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1110/ps.03449904
Volume 13
Issue 4
Start page 992
End page 999
Total pages 8
Place of publication Woodbury
Publisher Cold Spring Harbor Lab Press, Publications Dept
Language eng
Abstract A novel method for the refinement of misfolded protein structures is proposed in which the properties of the solvent environment are oscillated in order to mimic some aspects of the role of molecular chaperones play in protein folding in vivo. Specifically, the hydrophobicity of the solvent is cycled by repetitively altering the partial charges on solvent molecules (water) during a molecular dynamics simulation. During periods when the hydrophobicity of the solvent is increased, intramolecular hydrogen bonding and secondary structure formation are promoted. During periods of increased solvent polarity, poorly packed regions of secondary structures are destabilized, promoting structural rearrangement. By cycling between these two extremes, the aim is to minimize the formation of long-lived intermediates. The approach has been applied to the refinement of structural models of three proteins generated by using the ROSETTA procedure for ab initio structure prediction. A significant improvement in the deviation of the model structures from the corresponding experimental structures was observed. Although preliminary, the results indicate computationally mimicking some functions of molecular chaperones in molecular dynamics simulations can promote the correct formation of secondary structure and thus be of general use in protein folding simulations and in the refinement of structural models of small- to medium-size proteins.
Keyword Biochemistry & Molecular Biology
protein structure prediction
homology modeling
molecular dynamics
structure refinement
chaperone
Structure Prediction
Models
Stability
Mechanism
Machines
Genomics
Systems
Design
Domain
Decoys
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 20 Sep 2007, 04:10:44 EST